Effects of Ethamivan in Patients with Chronic Respiratory Disease

Nineteen patients suffering from chronic respiratory disease were evaluated before, during and after ethamivan administration by serial measurement of arterial pH, pCO₂, plasma ethamivan levels and alveolar ventilation. Ethamivan was administered intravenously as a single injection of 50 mg. in five patients; as an injection of 25 mg./kg. in five patients; as an intravenous injection of (a) 50 mg. over 15 minutes and (b) 150 mg. over 15 minutes in five patients; and finally as an oral dose of 300 to 500 mg. in five patients.Plasma levels of ethamivan became unmeasurable within 15 minutes of receiving the largest dose. Alveolar ventilation increased only in patients receiving the highest intravenous dose, and no significant changes in blood gases were elicited in any patient.     

Barbiturate Intoxication: Morbidity and Mortality

The complications encountered in caring for 185 patients intoxicated with barbiturates were reviewed. The population consisted of 142 patients with long-acting barbiturate concentrations of 8 mg per 100 ml or greater, 20 patients with short-acting barbiturate concentrations of 3 mg per 100 ml or greater and 23 consecutive patients with short-acting barbiturate intoxication referred for monitoring. Pneumonia was the major cause of morbidity and mortality and correlated best with the initial depth of coma and the use of an endotracheal tube in treatment. Cardiovascular instability manifested by pulmonary edema was the next leading cause of morbidity and mortality and correlated best with the initial depth of coma and the quantity of intravenous fluid administered. In retrospect, use of eliminative measures such as dialysis would probably not have altered the outcome in most of the patients who died and attempts at forced diuresis may have contributed to several deaths. Particular emphasis should be placed on the problems of sepsis and fluid therapy in the management of these patients.     

A BARBITURATE ANTIDOTE—Use of Methylethylglutarimide in Barbiturate Intoxication and in Terminating Barbiturate Anesthesia

Methylethylglutarimide was administered to 488 patients ranging in age from 7 to 89 years, in a study on sleep-reversal after harbiturate anesthesia. Sodium surital or sodium pentothal were the barbiturates used. The drug was administered intravenously in doses varying from 25 to 200 mg. Dosage below 25 mg. was found to be ineffective. Almost all patients showed signs of awakening as evidenced by the return of corneal and conjunctival reflexes, the opening of the eyes, and stirring or moving about. Many responded to questioning. Almost all showed evidence of greater responsiveness within five minutes. No untoward reactions were noted. No convulsions were produced.Five patients ranging in age from 24 to 70 years were treated for barbiturate poisoning with Mikedimide® given intravenously in doses varying from 550 mg. to 1950 mg. All recovered consciousness within 30 minutes to an hour. No convulsions were produced.While it is not known whether Mikedimide is a direct barbiturate antagonist, or whether it is an analeptic, it appears to be a useful drug in reversing the respiratory depression and the cerebral depression produced by harbiturate intoxication and barbiturate anesthesia.     

Respiratory and cardiovascular responses resulting from intravenous injection of sheep hydatid cyst fluid to dogs

Effects of intravenous injection of sheep hydatid cyst fluid on respiratory and cardiovascular systems were studied in sodium pentobarbital-anesthetized dogs. Under sterile conditions, the fluid was drawn from the liver and lung hydatid cysts of sheep, and centrifuged for 20 min at 500g. The supernatant fluid was used as the test solution. In a majority of animals, administration of 5 ml of the cyst fluid caused a sharp fall in arterial blood pressure, with or without respiratory changes. The latter, when present, included temporary cessation of respiration followed by rapid shallow breathing. There was usually an increase in the heart rate as the arterial blood pressure dropped. Atropine, 0.5 mg/kg body wt, given subcutaneously prior to the cyst fluid administration, did not block the responses. Cardiovascular responses produced by intravenous injection of cyst fluid were similar in dogs with positive pressure breathing and with spontaneous breathing. In 7 out of 10 responsive dogs, pretreatment with the antihistamine, chlorpheniramine, abolished the respiratory and cardiovascular responses.     

Nonuniform spatial patterns of respiratory activity within biofilms during disinfection.

Fluorescent stains in conjunction with cryoembedding and image analysis were applied to demonstrate spatial gradients in respiratory activity within bacterial biofilms during disinfection with monochloramine. Biofilms of Klebsiella pneumoniae and Pseudomonas aeruginosa grown together on stainless steel surfaces in continuous-flow annular reactors were treated with 2 mg of monochloramine per liter (influent concentration) for 2 h. Relatively little biofilm removal occurred as evidenced by total cell direct counts. Plate counts (of both species summed) indicated an average 1.3-log decrease after exposure to 2 mg of monochloramine per liter. The fluorogenic redox indicator 5-cyano-2,3-ditolyl tetrazolium chloride (CTC) and the DNA stain 4',6-diamidino-2-phenylindole (DAPI) were used to differentiate respiring and nonrespiring cells in biofilms. Epifluorescence micrographs of frozen biofilm cross sections clearly revealed gradients of respiratory activity within biofilms in response to monochloramine treatment. These gradients in specific respiratory activity were quantified by calculating the ratio of CTC and DAPI intensities measured by image analysis. Cells near the biofilm-bulk fluid interface lost respiratory activity first. After 2 h of biocide treatment, greater respiratory activity persisted deep in the biofilm than near the biofilm-bulk fluid interface.     

Evaluation of the usefulness of forced diuresis in patients with calcium cyclobarbital or reladorm poisoning

An attempt was made at evaluating the usefulness of forced diuresis for the treatment of Phanodorm poisoning. Fifty two patients were examined, 40 of them with Reladorm (Polish trade name. Reladorm contains 100 mg of cyclobarbital and 10 mg of diazepam) poisoning and 12 with Cyclobarbitalum Calcium (Phanodorm) poisoning. The test group was selected out of those poisoned with barbiturates so that a homogeneous toxic agent would be involved and the impact that other toxins may have on the rate of metabolism and excretion eliminated. The elimination of drug from blood was compared with the elements determining ED intensity, such as i.v. fluid administration, primary infiltrate (clearance of endogenous creatinine), reabsorption in renal tubules and diuresis rate. No correlation was found which is an evidence that ED proves to be useless in the treatment of Phanodorm poisoning. The author suggests that in this type of poisoning supportive treatment should be undertaken according to daily fluid demand in relation to such factors as sex, age, body temperature, health conditions and contraindications due to the patient's general condition.     

Respiratory effects of analgesia after cholecystectomy: comparison of continuous and intermittent papaveretum.

Two methods of administering papaveretum for relieving postoperative pain were compared in two groups of patients who had undergone cholecystectomy. In one group a loading dose of papaveretum was administered by continuous intravenous infusion (1 mg/min) until the patient could breathe deeply without undue pain. Eight times this loading dose was given as a continuous intravenous infusion over the subsequent 48 hours. This regimen was compared with a conventional intermittent intramuscular dose (0.25 mg/kg at four hourly intervals as necessary) in a second group of patients. The intravenous regimen relieved pain better than the intramuscular regimen, which may have reflected the larger dose of papaveretum given to the intravenous group, but it was accompanied by a greater degree of respiratory depression and potentially life-threatening changes in respiratory pattern. These findings suggest that the fear which often accounts for inadequate postoperative pain relief-that larger dose of analgesics will cause respiratory complications-is well founded.     

Acute drug poisoning in the adult

In a prospective study of 349 patients with acute poisoning treated at The Montreal General Hospital in 1972 benzodiazepines and non-barbiturate hypnotics were found to be the most frequent putative drugs. Of the 108 patients admitted to hospital 37% had taken an overdose of a drug prescribed for them by their psychiatrist or other physician; 48% had formerly taken an overdose of drugs and 44% had had previous psychiatric treatment. Unconsciousness, respiratory depression, metabolic acidosis and acidemia, and hypokalemia were the most frequent clinical abnormalities observed. Treatment was supportive. There were six deaths. The average duration of coma was short; only five surviving patients remained unconscious for more than 24 hours. Respiratory complications were frequent.It is recommended that more attention be paid to recognizing patients whose behaviour pattern might include such an impulsive gesture, and that alternatives be found for barbiturate and non-barbiturate hypnotics.     

Pathological consequences of low atmospheric pressure stunning in broiler chickens

Low atmospheric pressure stunning (LAPS) is a novel approach to pre-slaughter stunning of chickens using progressive hypobaric hypoxia by the application of gradual decompression (280s cycle) according to a set of prescribed pressure curves. Low atmospheric pressure stunning produces a non-recovery state. Concerns have been raised relating to the possible pathological and welfare consequences of expansion of air in the body during LAPS. In a randomised trial, we compared the gross pathology of broilers exposed to LAPS with a control group euthanised by intravenous injection of pentobarbital sodium (60 mixed sex broilers per treatment). The birds were exposed to each treatment in triplets and all birds were subject to necropsy examination to detect and score (1 to 5, minimal to severe) haemorrhagic lesions or congestion for all major organs and cavities (e.g. air sacs, joints, ears and heart) as well as external assessment for product quality (e.g. wing tips). Behavioural data (latency to loss of posture and motionless) and chamber cycle data (temperature, humidity, pressure and oxygen availability) confirmed that LAPS had been applied in a manner representative of the commercial process. All of the organs observed were structurally intact for both treatment groups. No lesions were observed in the external ears, oral cavity, tracheal lumen, crop and air sacs of birds from either treatment group. There was no difference between treatments in the wingtips, nasal turbinates, thymus, biceps femoralis and colon. Haemorrhagic lesions were observed in the calvaria, brains, hearts and lungs of both treatment groups, but lesions in these areas were more severe in the LAPS treatment group. It was not possible to distinguish between pathological changes induced by decompression or recompression. In the barbiturate group, more severe haemorrhagic lesions were observed in the superficial pectoral muscles as well as greater congestion of the infraorbital sinuses, liver, spleens, duodenum, kidneys and gonads. These findings provide evidence that LAPS did not result in distension of the intestines and air sacs sufficient to cause changes, which were grossly visible on postmortem examination. There was also no evidence of barotrauma in the ears and sinuses. The pathological changes observed in the barbiturate treatment were as expected based on barbiturate toxicity. Low atmospheric pressure stunning appears to produce pathological changes by a variety of well-established mechanisms, and while these pathological data have limited value as welfare indicators, the results confirm that organ integrity was not compromised by the process.     

Iatrogenic hyponatraemia of the newborn due to maternal fluid overload: a prospective study.

Over five weeks 136 out of 246 deliveries were studied. Maternal plasma sodium concentrations were normal at admission. At delivery no significant difference was found between maternal and infant cord plasma sodium concentrations. Twenty-four of the 41 mothers who had received only oral fluids during labour had infants whose cord plasma sodium concentrations were normal. Of the 95 mothers who had been given intravenous fluids, however, only 14 infants with normal plasma sodium concentrations, 31 had a concentrations of 130 mmol (mEq)/1 or less and nine of these had a concentration of 125 mmol/1 or less. There was a highly significant inverse relation between cord plasma sodium concentration and rate of fluid administration, suggesting that hyponatraemia was due to intravenous treatment with predominantly sodium-free solutions. Endogenous antidiuretic activity probably increases during labour, and synthetic oxytocin in large doses has been shown to have an antidiuretic effect. The dose used in this study did not appear to have such an effect. Glucose solutions are often used as a vehicle for oxytocin; 83% of all fluid intake in this study was 5% or 10% glucose in water. Fluid balance in labour should be supervised closely, and oxytocin should be given in a more concentrated solution.     

Effect of indomethacin on prostaglandin content of several rabbit tissues

The prostaglandin (PG) content of several tissues and fluids from 6 day pregnant rabbits was evaluated following treatment with indomethacin or vehicle . PGE and PGF were measured by radioimmunoassay. More complete depletion of PGE and PGF was accomplished by 3 injections of indomethacin (s.c.) given during the 18 h before sacrifice at a dose of 10 mg indomethacin per kg body weight than was accomplished by 1 injection of the same amount of indomethacin (i.v.) 1.5 h before sacrifice. Levels of PGF were more easily depressed by indomethacin than were those of PGE. PG levels in the kidney and blastocysts were depressed to a greater extent by indomethacin than were those in the uterus, uterine fluid or peritoneal fluid. Evaluation of the effect of indomethacin on a particular physiological function should be interpreted with caution unless the extent of PG depletion in that tissue is also measured.     

Effect of indomethacin in vivo on prostaglandin content of several rabbit tissues

The prostaglandin (PG) content of several tissues and fluids from 6 day pregnant rabbits was evaluated following treatment with indomethacin or vehicle in vivo. PGE and PGF were measured by radioimmunoassay. More complete depletion of PGE and PGF was accomplished by 3 injections of indomethacin (s.c.) given during the 18 h before sacrifice at a dose of 10 mg indomethacin per kg body weight than was accomplished by 1 injection of the same amount of indomethacin (i.v.) 1.5 h before sacrifice. Levels of PGF were more easily depressed by indomethacin than were those of PGE. PG levels in the kidney and blastocysts were depressed to a greater extent by indomethacin than were those in the uterus, uterine fluid or peritoneal fluid. Evaluation of the effect of indomethacin on a particular physiological function should be interpreted with caution unless the extent of PG depletion in that tissue is also measured.     

The efficacy of cefepime (Maxipime) in the treatment of abdominal sepsis in surgical patients]

The efficacy of cefepime in the treatment of 46 patients operated for general peritonitis of various genesis and severity (APACHE II not greater than 35) was studied. Cefepime was used in a dose of 2 g administered every 12 hours as slow intravenous infusions in 0.9 per cent sodium chloride solution in combination with metronidazole administered intravenously in a dose of 7.5 mg/kg body weight. The treatment course was 4 to 15 days. 45 patients were given diflucan for the prophylaxis of fungal superinfection, 3 patients were given aminoglycoside antibiotics (netilmicin or amikacin) and 2 patients were given vancomycin per os. The favourable clinical effect of the cefepime therapy was stated in 38 patients (82.6 per cent) including 4 out of 10 patients with initial APACHE II > 15. 101 isolates of aerobic gram-negative and gram-positive microbes from 38 patients treated with cefepime in combination with metronidazole were tested to estimate the bacteriological efficacy of the therapy and it was shown that only 5.9 per cent of them was resistant. The pathogen eradication was stated in 84.2 per cent of the patients.     

Management of respiratory complications in a western lowland gorilla (Gorilla gorilla gorilla) born by cesarean section

A female western lowland gorilla (Gorilla gorilla gorilla) infant was delivered by cesarean section (C‐section) to an 18‐year‐old primiparous dam after prolonged labor. The infant required resuscitation at birth and was hospitalized for management of pneumonia and associated respiratory distress secondary to the aspiration of meconium‐stained amniotic fluid. The infant received nine days of intensive care with respiratory support, antibiotics, intravenous fluid therapy, anti‐inflammatory drugs, bronchodilators, and chest physiotherapy. Respiratory support included nasal continuous positive airway pressure (CPAP), and supplemental oxygen. Complications included right lung atelectasis secondary to bronchial obstruction and pneumonia. Following the resolution of pneumonia, visual reintroductions with the troop were initiated. The dam was given a medical lactation supplement (metoclopramide) and her mammary glands were stimulated to increase milk production. After several days of visual and olfactory introductions, the infant was successfully physically reintroduced to her dam at 12 days of age; the dam showed appropriate maternal response and nursing of the infant. The infant had appropriate growth and development, and 4 years later, has no evidence of negative side effects of neonatal respiratory disease. This is the first reported case of management of neonatal gorilla respiratory disease associated with a C‐section, with successful reintroduction to the family group after hospitalization.     

Breathing pattern and CO2 response in newborn rats before and during anesthesia

We have studied the breathing pattern (minute ventilation VE, tidal volume VT, and respiratory rate f) in newborn rats before and during barbiturate (20-30 mg/kg ip) or ketamine anesthesia (40-80 mg/kg ip). Animals were intact and prone in a flow plethysmograph in thermoneutral conditions. Before anesthesia, CO2 breathing (5 min in 5% and 5 min in 10% CO2 in O2) resulted in a substantial increase in VE (169 and 208%, respectively), which was maintained throughout the entire CO2 breathing period. This indicates that, despite the extremely large VE per kilogram at rest, in these small animals there is still a large reserve for a sustained increase in VE. During barbiturate, the resting VE dropped to 45% of control, due to a reduction in VT (83%) and f (59%). This latter result was due to a prolongation of the expiratory time (214%) with no significant changes in inspiratory time. CO2 response was also much depressed, to approximately 63% of the control. The late portion of the expiratory flow-volume curves, the slope of which represents the expiratory time constant of the system, was similar before and during anesthesia in approximately 50% of the animals, whereas it increased during anesthesia in the remaining animals. Although compliance of the respiratory system was generally unaltered, the increased impedance during anesthesia probably reflected an increased resistance. Qualitatively similar results were obtained during ketamine anesthesia. Therefore, as observed in adult mammals, anesthesia in newborn rats has a marked depressant effect on resting breathing pattern and CO2 response, occasionally accompanied by an increase in the expiratory impedance of the respiratory system.     

Paget's disease of bone: early and late responses to three different modes of treatment with aminohydroxypropylidene bisphosphonate (APD).

Early and late responses to treatment with either oral (600 mg/day) or intravenous (20 mg/day) (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (aminohydroxypropylidene bisphosphonate; APD) were studied in 142 patients with Paget''s disease of bone who had not previously been treated with bisphosphonate. The efficacy of three therapeutic regimens was compared: (a) oral aminohydroxypropylidene bisphosphonate given continuously until six months after the serum alkaline phosphatase activity had returned to normal (long term); (b) oral aminohydroxypropylidene bisphosphonate given until urinary hydroxyproline excretion had returned to normal (short term); (c) intravenous aminohydroxypropylidene bisphosphonate for 10 days. With either oral or intravenous treatment the decrease in urinary hydroxyproline excretion was rapid and always preceded the fall in serum alkaline phosphatase activity. Normal urinary hydroxyproline excretion is essential for return of the serum alkaline phosphatase activity to normal. Complete biochemical remission, defined as return of the serum alkaline phosphatase activity to normal, was obtained in 129 patients (91%). The median duration of remission as assessed by actuarial analysis was 2.7 years. This study found no difference in the long term among the three modes of treatment, suggesting that for most patients with Paget''s disease a short course of intravenous aminohydroxypropylidene bisphosphonate will produce longlasting, complete remission without need for maintenance treatment.     

Effect of pyracetam on fatigue of inspiratory muscles in cats

The aim of the work was to study the influence of pyracetam on respiratory muscles fatigue and ventilatory disorders caused by inspiratory resistive load in cats. The experiments have show that after the use of pyracetam in conditions of fatigue total bioelectric activities of inspiratory muscles and of the phrenic nerve and transdiaphragmal pressure restore; duty cycle, respiratory rate and tidal volume per minute decrease. The conclusion is drawn that pyracetam in the dose 300 mg/kg, in intravenous administration, compensates inspiratory muscle fatigue at the expense of its central mechanism of action.     

Occurrence of Coagulase-Positive Staphylococci in Cheddar Cheese

Samples (13) from several lots of cheddar cheese incriminated in staphylococcal food poisoning and 343 samples of cheddar cheese purchased over a 3-year period in retail markets were examined quantitatively for coagulase-positive staphylococci with the smear plate technique. Of the food-poisoning samples, 11 contained coagulase-positive staphylococci in numbers that ranged from 50 to several million per g. Of the 343 market cheese samples, 20% contained coagulase-positive staphylococci in concentrations ranging from less than 50 to more than 200,000 per g. The phage patterns of 64 of 89 cultures isolated from the food-poisoning samples placed them in the miscellaneous phage group (44A) or in phage group IV and the miscellaneous group (42D/44A); 14 had phage patterns that involved group III, the group with which food poisoning has usually been associated. In contrast, over 50% of 104 cultures from the market cheese, which were typed at 100 times the critical test dilution, had phage patterns that involved group III. Of nine selected cultures isolated from the food-poisoning cheese, three (all in phage group III) were positive for enterotoxin by intravenous injection test of cats.     

Erythromycin penetration into the cerebrospinal fluid of patients]

Permeability of erythromycin through the barrier of blood-cerebrospinal fluid in neurosurgical patients after its oral administration in a dose of 300-500 mg and intravenous administration in a dose of 200 mg was studied. The erythromycin was determined after the antibiotic single administration at intervals of 40 minutes to 6 hours. A total of 31 observations were performed. Low penetration of erythromycin into the cerebrospinal fluid of the patients was shown. The administration route (oral or intravenous) practically had no effect on the antibiotic penetration level into the subarachnoidal spaces. The highest liquor levels were observed within the period of 3 to 6 hours after the drug administration. The maximum index of penetration from the blood into the cerebrospinal fluid was about 10 per cent. The erythromycin penetration increased in cases with inflammatory changes in the meninges.